Weight, age and coefficients of variation in renal solute excretion

Homoscedasticity (constant variance over axes or among statistical factors) is an integral assumption of most statistical analyses. However, a number of empirical studies in model organisms and humans demonstrate significant differences in residual variance (that component of phenotype unexplained by known factors) or intra-individual variation among genotypes. Our work suggests that renal traits may be particularly susceptible to randomization by genetic and non-genetic factors, including endogenous variables like age and weight.

We tested associations between age, weight and intra-individual variation in urinary calcium, citrate, chloride, creatinine, potassium, magnesium, sodium, ammonium, oxalate, phosphorus, sulfate, uric acid and urea nitrogen in 9,024 male and 6,758 female kidney stone patients. Coefficients of variation (CVs) were calculated for each individual for each solute from paired 24-hour urines. Analysis of CVs was corrected for inter-measurement collection variance in creatinine and urine volume. CVs for sodium and urea nitrogen were included to correct for dietary salt and protein.

Age was positively associated with individual CVs for calcium and negatively associated with CVs for potassium, ammonium and phosphorus (p(FDR) < 0.01). Weight was associated with CVs for creatinine, magnesium and uric acid, and negatively associated with CVs for calcium, potassium and oxalate (p(FDR) < 0.05).

Intra-individual variation changes over age and weight axes for numerous urinary solutes. Changing residual variance over age and weight could cause bias in the detection or estimation of genetic or environmental effects. New methodologies may need to account for such residual unpredictability, especially in diverse collections.